Identification of berbamine dihydrochloride from barberry as an anti-adipogenic agent by high-content imaging assay

Objective:Lipid droplet(LD)deposition in adipose tissue is a critical factor leading to metabolic dysfunction.Various herbal medicines in traditional Chinese medicine(TCM)are used to treat hyperlipidemia,type 2 diabetes,obesity,and other diseases.The objective of this study was to identify potential anti-adipogenic agents from TCM herbal compounds.Methods:One hundred and twenty compounds were evaluated in terms of their effect on adipocyte differentiation through image-based high content screening.Anti-adipogenic effects of identified hits were further confirmed at various concentrations.In addition,drug-induced liver injury assay was performed with HepG2 cells to test the hepatotoxicity of hit compounds.Results:Berbamine(BBM),a chemical isolated from barberry,and a derivative of BBM,berbamine dihydrochloride(BBMD),reduced LDs formation by more than 50%.Dose-dependent effects were observed and the IC50 values of the two hits,BBM and BBMD,were determined as 1.88 mM and 0.95 mM,respectively.Moreover,BBM induced mild HepG2 cell injury,while its dihydrochloridedBBMD did not exhibit hepatotoxicity within 40 mM.Conclusion:This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.

Effect of Trimetazidine Dihydrochloride Tablets adjuvant therapy on inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function in patients with coronary heart disease complicated with heart failure

Objective: To investigate the effects of Trimetazidine Dihydrochloride Tablets on inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function in patients with coronary heart disease complicated with heart failure. Methods: A total of 98 patients with coronary heart disease and heart failure who met the criteria of the study were selected as the subjects, based on the random data table they were divided into the control group (n=49) and observation group (n=49), the patients in the control group were treated with Metoprolol Tartrate Sustained-release Tablets treatment, and the patients in the observation group were treated with Metoprolol Tartrate Sustained-release Tablets combined with Trimetazidine Dihydrochloride Tablets, the levels of inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function indexes were compared between the two groups before and after treatment. Results: The difference of the CRP, TNF-α, MDA, SOD, NO, ET-1, LVEF, LVEDD and LVESD levels in the two groups before treatment were not statistically significant;Compared with the levels of the two groups before treatment, the two groups of CRP, TNF-α, MDA, ET-1, LVEDD and LVESD levels after treatment were significantly decreased, and the level of the observation group after treatment was significantly lower than those levels in the control group, the difference was statistically significant;The levels of SOD, NO and LVEF of the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group levels [(88.09±7.51) U/ml, (72.58±14.64) mol/L, (48.34±5.09)% ] were significantly higher than the control group [(79.44±7.27) U/ml, (61.89±11.06) mol/L, (44.19±4.58)%], the difference was statistically significant. Conclusion: Trimetazidine Dihydrochloride Tablets in the treatment of coronary heart disease with heart failure can effectively inhibit the release of inflammatory factors, improve oxidative stress state, vascular endothelial function and myocardial function, has an important clinical value.

Determination of Camylofin Dihydrochloride and Nimesulide in Pharmaceutical Preparation by Gas Chromatography

This research paper describes simple analytical method for determination of Camylofin dihydrochloride and Nimesulide in tablet formulation by Gas chromatography method. Benzoic acid was used as internal standard. Validation was carried out in compliance with the International Conference on Harmonization guidelines. The method utilized GC (Agilent Technologies 6890 N Network GC system with FID detector), and RTX-5 capillary column (5% diphenyl-95% dimethyl polysiloxane), 30 m × 0.53 mm, 1.5 μm as stationary phase. Helium was used as the carrier gas at a flow rate of 1.5 mL?min–1. The proposed method was validated for linearity, LOD, LOQ, accuracy, precision, ruggedness and solution stability. It can be conveniently adopted for routine quality control analysis.

抗丙肝新药daclatasvir dihydrochloride的合成

目的:合成抗丙肝新药daclatasvir dihydrochloride,并对其工艺进行改进。方法:以联苯为原料经傅克酰基化,亲核取代,环合,酸化脱保护和亲核取代反应制得daclatasvir dihydrochloride。结果:目标产物结构经1H-NMR和MS确证,整个工艺总收率为23.9%。结论:本路线操作简便、成本较低、条件温和、步骤少,适合工业化生产。

Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination

Objective：To investigate the effects of E7080 and N5-（1-iminoethyl）-L-ornithine dihydrochloride （L-NIO）on colorectal cancer alone and in combination.Methods：HT29 colorectal cancer cell line from Sap Institute was used.Real-time cell analysis （xCELLigence system） was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation.While apoptosis was determined with Annexin V staining,and the effect of agents on angiogenesis was determined with chorioallantoic membrane （CAM） model.Results：We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration （IC50） value of 5.60×10-8 mol/L.Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells.Antiangiogenic scores of E7080 were 1.2,t.0 and 0.6 for 100,10 and 1 nmol/L E7080 concentrations,respectively.Furthermore,apoptosis has been detected in 71％ of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect.Meanwhile administration of L-NIO alone did not show any effect,but the combination of E7080 with L-NIO increased the antiproliferative,antiangiogenic and apoptotic effects of E7080.Conclusions：Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors.Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080.

PREPARATION AND CHARACTERIZATION OF AFFINITY POLYMER BASIC MICROSPHERES BY SOAP-FREE EMULSION POLYMERIZATION

Poly(styrene-co-glycidyl methacrylate) latex microspheres with uniform size and high-density epoxy groups on the surface were prepared by soap-free emulsion polymerization with batch wise operation mode in the presence of 2.2′- azobis(2-methylpropionamidine) dihydrochloride as an initiator.The kinetics of soap-free emulsion polymerization and the effects of polymerization factors were examined.In addition,the optimum polymerization conditions of poly(styrene-co- glycidyl methacrylate) latex microspheres for...

Studies on the Synthesis and Electron Spectra of 2,6-Bis(p-Aminophenyl)Benzo[1,2-d;5,4-d']Bisoxazole

A novel method to synthesize 2,6-bis(p-aminophenyl)benzo\[1,2-d;5,4-d'\]bisoxazole using 1,2,3-trichlorobenzene as the starting material through nitration, substitution, hydrogenation, and condensation was reported. During the condensation, the influence of the amount of SnCl_2 on the yield of the product was studied. The electron spectra of the compound were discussed, the results showed that it is a fluorescence material with large Stokes shift.

Feeding of grey squirrels (Sciurus carolinensis) with the contraceptive agent DiazaCon^(TM):effect on cholesterol, hematology, and blood chemistry

Grey squirrels(Sciurus carolinensis)are an invasive species in Britain and Italy.They have replaced native red squirrels(Sciurus vulgaris)throughout most of Britain,and cause damage to trees.Currently,lethal control is used to manage grey squirrel populations in Britain,but nonlethal methods might be more acceptable to the public.One such method is contraception with 20,25-diazacholesterol dihydrochloride(DiazaCon^(TM)).DiazaCon^(TM) inhibits the conversion of desmosterol to cholesterol,resulting in increasing desmosterol concentrations and decreasing cholesterol concentrations.Because cholesterol is needed for the synthesis of steroid reproductive hormones,such as progesterone and testosterone,inhibition of cholesterol synthesis indirectly inhibits reproduction.Desmosterol is used as a marker of efficacy in laboratory studies with species that do not reproduce readily in captivity.Grey squirrels were gavaged with a DiazaCon^(TM) solution for 2 days,and then fed DiazaCon^(TM)-coated peanuts for an additional 8 days at target doses of 50 and 100 mg DiazaCon^(TM) per kg body weight.There was a significant difference in cholesterol concentrations in the treatment groups compared to the control group.Cholesterol was reduced by≥40%for 2 months in both treatment groups.There were no differences among groups with respect to blood chemistry and hematology parameters,and mean values are reported.The mean overall dose of DiazaCon^(TM) received was 29.0±1.6 and 55.3±4.3 mg/kg in the low(50 mg/kg)and high dose(100 mg/kg)groups,respectively.DiazaCon^(TM) might provide an effective,acceptable alternative to lethal control.